Tumor hypoxia, observed in all types of human tumors, is an independent prognosticator of malignant progression and poor patient survival. The conventional wisdom is that hypoxic tumor cells are resistant to conventional therapy and is highly metastatic. Therefore, targeting hypoxic tumor cells has inevitably become a focus of current cancer treatment plans as well as drug development efforts. Unfortunately, there remains a lack of definitive answers about the true malignant phenotypes and characteristics of hypoxic tumor cells in vivo, which partly explains the lack of convincing benefits of targeting hypoxic tumor cells in clinical trials so far. To addrss these pertinent questions, we propose an innovative approach to specifically mark hypoxic cells for in vivo identification or ex vivo isolation, as well as to follow their metastatic journey and o monitor cell fate after anti-cancer treatment in vivo. We will also use this innovative strategy to conduct targeted investigation of signaling pathways specifically in hypoxic cells in vivo without the unwanted interference from the adjacent non-hypoxic tumor cells.

Public Health Relevance

The project will provide direct in vivo evidence about the contribution of hypoxic tumor cells to malignant progression and therapy resistance, which will have a tremendous impact on how hypoxic tumors should be treated in clinics. The new methodology developed in this application will have the potential to positively change the way hypoxia research is conducted in the future.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01CA178254-01A1
Application #
8774043
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Bernhard, Eric J
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06510